The invention relates to a process for producing nanoparticles, i.e. particles essentially consisting of a biopolymer such as starch. The invention also relates to nanoparticles obtainable by such a process.
U.S. Pat. No. 5,116,890 discloses self-crosslinking latices on the basis of a starch emulsion polymer graft. These latices require undesirable chemicals and are too hydrophobic for many applications.
It was found that biopolymers such as starch and other polysaccharides such as cellulose and gums, as well as proteins (e.g. gelatin, whey protein) can be formed into nanoparticles by processing the biopolymer using shear forces and simultaneous cross-linking. The biopolymers may be previously modified, e.g. with cationic groups, carboxy-methyl groups, by acylation, phosphorylation, hydroxyalkylation, oxidation and the like. Starch and mixtures of starch with other (bio)polymers containing at least 50% starch are preferred. The biopolymer preferably has a dry substance content of at least 50%, especially at least 60% by weight at the time when processing starts.
Processing using shear forces according to the invention means a mechanical treatment, which is in particular an extrusion treatment performed at elevated temperature (above 40xc2x0 C., especially above 60xc2x0 C., below the degradation point of the polymer, up to e.g. 200xc2x0 C., especially up to 140xc2x0 C.) under conditions of high shear. The shear can be effected by applying at least 100 J of specific mechanical energy (SME) per g of biopolymer. Depending on the processing apparatus used the minimum energy may be higher; also when non-pregelatinised material is used, the minimum SME may be higher, e.g. at least 250 J/g, especially at least 500 J/g.
The mechanical treatment is conveniently performed at elevated temperature. The elevated temperature may be moderated, in case of starch, by using an alkaline medium or by using pregelatinised starch. During the mechanical treatment, the biopolymer is present in high concentration, especially a concentration of at least 40, more preferably at least 50 wt. %, in an aqueous solvent, such as water or a water/alcohol mixture. High pressure (e.g. between 5 and 150 bar) may be applied to facilitate processing at high concentrations.
A plasticiser may be present in addition to the water or water/alcohol mixture, such as a polyol (ethyleneglycol, propyleneglycol, polyglycols, glycerol, sugar alcohols, area, citric acid esters, etc.) at a level of 5-40% by weight of the biopolymer. However, water can already act as a plasticiser. The total amount of plasticisers (i.e. water and other such as glycerol) is preferably between 15 and 50%. A lubricant, such as lecithin, other phospholipids or monoglycerides, may also be present, e.g. at a level of 0.5-2.5% by weight. An acid, preferably a solid or semi-solid organic acid, such as maleic acid, citric acid, oxalic, lactic, gluconic acid, or a carbohydrate-degrading enzyme, such as amylase, may be present at a level of 0.01-5% by weight of biopolymer; the acid or enzyme assists in slight depolymerisation which is assumed to be advantageous in the process of producing nanoparticles of a specific size.
An essential step in the process of the invention is the crosslinking during the mechanical treatment. The crosslinking is preferably reversible, i.e. the crosslinks are partly or wholly cleaved after the mechanical treatment step. Suitable reversible crosslinkers include those which form chemical bonds at low water concentrations, which dissociate or hydrolyse in the presence of higher water concentrations. This mode of crosslinking results in a temporary high viscosity during processing followed by a lower viscosity after processing.
Examples of reversible crosslinkers are dialdehydes and polyaldehydes, which reversibly form hemiacetals, acid anhydrides and mixed anhydrides (e.g. succinic and acetic anhydride) and the like. Suitable dialdehydes and polyaldehydes are glutaraldehyde, glyoxal, periodate-oxidised carbohydrates, and the like. Glyoxal is a particularly suitable crosslinker for the purpose of the invention.
Such crosslinkers may be used alone or as a mixture of reversible crosslinkers, or as a mixture of reversible and non-reversible crosslinkers. Thus, conventional crosslinkers such as epichlorohydrin and other epoxides, triphosphates, divinyl sulphone, can be used as non-reversible crosslinkers for polysaccharide biopolymers, while dialdehydes, thiol reagents and the like may be used for proteinaceous biopolymers. The crosslinking reaction may be acid- or base-catalysed. The level of crosslinking agent can conveniently be between 0.1 and 10 weight % with respect to the biopolymer. The crosslinking agent may already be present at the start of the mechanical treatment, but in case of a non-pre-gelatinised biopolymer such as granular starch, it is preferred that the crosslinking agent is added later on, i.e. during the mechanical treatment.
The mechanically treated, crosslinked biopolymer is then formed into a latex by dispersion in a suitable solvent, usually water and/or another hydroxylic solvent such as an alcohol), to a concentration of between 4 and 50 wt. % especially between 10 and 40 wt. %. Prior to the dispersion a cryogenic grinding step may be performed, but stirring with mild heating may work equally well. This treatment results in a gel which either spontaneously or after induction by water adsorption, is broken into a latex. This viscosity behaviour can be utilised for applications of the particles, such as improved mixing, etc. If desired, the dispersed biopolymer may be further crosslinked, using the same or other crosslinking agents as describe above.
The invention pertains to an extrudate obtained by plasticising a biopolymer, in particular starch, and crosslinking it as described above. The extrudate is characterised by swelling in an aqueous solvent, e.g. water or a mixture of at least 50% water with a water-miscible solvent such as an alcohol, and by exhibiting a viscosity drop afterwards to produce a dispersion of nanoparticles.
The invention also pertains to the nanoparticles obtainable from the extrudate referred to above. The nanoparticles (as such or as a dispersion) are characterised by their small particle size of below 400 nm, especially below 200 nm, their stability, narrow particle size distribution and viscosity. The narrow particle distribution is in particular reflected by the ratio of weight-averaged molecular weight to number-averaged molecular weight being below 2 (Mw/Mn less than 2).
The nanoparticles can be used as a matrix material i.e. as a resin e.g. in coating applications wherein an increased dry solids content is desired. Such matrix materials may be a film-forming material (for adjusting the minimum film-forming temperature), a thickener, or a rheology modifier, or an adhesive or an adhesive additive (tackifier). As a thickener, it may have higher viscosities, e.g. greater than 150 mPas. The nanoparticles or dispersions thereof may also be used for their barrier properties (high barrier for e.g. oxygen, low barrier e.g. for water), as a carrier (e.g. for colorants, medicaments, flavours and fragrances and the like, advantageously as a slow-release agent), as a fat replacer (due to their mouth-feel), in cosmetic compositions (lack of allergenic properties) etc., as a medicament for mitigating dermal disorders, bums and the like. Further examples of such applications are in the paper-making and packaging industry (paper and cardboard surface treatrnent, gloss etc.), or in agriculture and horticulture (protective layers on e.g. bulbs, and other plan t arts), or as removable or temporary coatings for protection purposes. The nanoparticles can also be used as excipients or carriers e.g. in medicines, where they may be complexed or covalently coupled to active substances such as slow-release drugs. The nanoparticles can also be processed into a foam at relatively high density.